P1112: PATIENT-REPORTED OUTCOMES (PRO) AMONG PATIENTS WITH MANTLE CELL LYMPHOMA RECEIVING PIRTOBRUTINIB AFTER PRIOR COVALENT BTKI: INTERIM PRO ANALYSIS FROM THE BRUIN PHASE 1/2 STUDY
Authors: Jonathon Cohen, Lindsey Roeker, Chan Cheah, Toby Eyre, Krish Patel, Jennifer Woyach, John Seymour, Michael Wang, Yucai Wang, Angely Loubert, Nalin Payakachat, Lisa Hess, Paolo Abada, Anthony R. Mato, Paolo Ghia
Journal: HemaSphere (2023)

Topic: 18. Indolent and mantle-cell non-Hodgkin lymphoma - Clinical Background: BRUIN 18001 (NCT03740529) is an ongoing, open-label, multi-center phase 1/2 study investigating the safety and efficacy of pirtobrutinib for the treatment of B-cell malignancies, including mantle cell lymphoma (MCL). Pirtobrutinib is a non-covalent (reversible) Bruton tyrosine kinase inhibitor (BTKi) that has recently received regulatory approval in the United States (US) for the treatment of patients with relapsed or refractory MCL after two or more lines of systemic therapy, including a covalent BTKi (cBTKi). Health-related quality of life (HRQoL) and patients’ symptom burden remain important considerations for making treatment decisions. Aims: This interim analysis summarizes patient-reported outcomes (PRO) among participants with relapsed or refractory MCL after prior cBTKi enrolled in the BRUIN study. Methods: PRO data were collected using paper forms at each clinic visit. HRQoL was collected using the EORTC QLQ-C30 (Physical Function and QoL subscales); patient-reported MCL symptoms data were from 13 EORTC Item Library (IL) items, and fatigue data were from 6 EORTC IL items. All subscales are scored 0-100. Pre-defined minimal clinically important difference (MCID) thresholds, defined as a minimum change in PRO scores that is clinically meaningful to patients for improvement or worsening, were used to categorize patients based on their individual change. Higher scores represent better Physical Functioning and QoL on those subscales. For MCL symptoms and fatigue, higher scores represent greater symptoms. Descriptive statistics were used to summarize interim PRO data from the cohort of patients with classic MCL who received prior cBTKi therapy. PRO data were presented from Cycle 1 to 11 since the majority of patients (84.7%) had duration of PFS <12 months. Results: A total of 124 patients with MCL were enrolled at the time of this interim analysis, with a mean (standard deviation [SD]) age of 69.4 (8.5) years, range: 46-88 years, at baseline. The majority were male (79.0%) and from the US (60.5%). The mean overall completion rate of PRO instruments was 85.5% at baseline. The proportion of enrolled participants completing subsequent assessments declined over time, at Cycle 11 the overall completion rate was 64.9%. Baseline mean (SD) Physical Function score was 83.6 (18.1) and QoL score was 62.6 (23.4). Mean (SD) MCL Symptoms and Fatigue scores at baseline were 21.2 (17.7) and 29.6 (23.1), respectively. The majority of patients reported stable or clinically meaningful improved outcomes from baseline for Physical Function (>80% of patients), QoL (>80%), MCL symptoms (>75%), and fatigue (>65%) at each of these visits (through Cycle 11), based on the MCID thresholds. Summary/Conclusion: Consistent with the favorable safety profile of pirtobrtuinib, HRQoL and symptoms were maintained or improved for the majority of R/R cBTKi exposed MCL patients throughout the first 11 cycles of pirtobrutinib treatment. PRO data should be interpreted with caution due to relatively small numbers of patients in later cycles and relatively low completion rates in some cycles. Keywords: Mantle cell lymphoma, Phase I/II, Patient reported outcomes, Bruton’s tyrosine kinase inhibitor (BTKi)